Spermicidal sheet-like material



United States Patent 3,108,043 SPERMICIDAL SHEET-LIKE MATERIAL NathanMillmau, Somerville, and Roger Edwin Homm,

N eshanic, NJ assignors to Ortho Pharmaceutical Corporation, acorporation of New Jersey No Drawing. Filed May 9, 1960, Ser. No. 27,5077 Claims. (Cl. 167-58) The present invention relates to a novel andimproved spermicidal manufacture for treatment of the vaginal cavity tobe acted on by the body fluids and provide a convenient and effectivespermicidal composition.

Objects and advantages of the invention will be set forth in parthereinafiter and in part will be obvious herefrom, or may be learned bypractice with the invention, the same being realized and attained bymeans of the steps, processes and compositions pointed out in theappended claims.

The invention consists in the novel steps, processes, compositions andimprovements herein shown and described.

The present invention has for its object the provision of a novel andimproved composition and article of manuiacture for the convenienttreatment of the vaginal cavity to provide it with a readily availableand regulated amount of a spermicidal material. A further object is theprovision of an economical and conveniently usable material which isadapted to dissolve at a controlled rate in the normal fluids availablein the vaginal cavity thereby supplying the cavity with a regulatedamount of spermicide. Still another object is the provisionv of a solidmaterial which is substantially 'dry, may be inexpensively packaged,which requires no apparatus for its 3,108,043 Patented Oct. 22, 1963 ice2 a suitable water soluble spermicide, such as a non-ionic detergent.

The weight ratio of spermicide to vehicle may be as great as 121. It hasbeen found that many spermicides are not compatible with the vehiclewhen present in larger quantities. The minimum amount of spermicidepresent should not be less than 5 milligrams per application. Thus, ifthe total weight of a single film or team designed for one applicationwere 720 milligrams, the minimum amount of spermicide present should notbe less than 5 milligrams. Another way of expressing this relationshipis that the weight ratio of spermicide to total solids is not less thanabout 1:145.

Any water soluble, non deleterious spermicide may be used, but thenon-ionic detergent spermicides are preferred and are selected from thegroup consisting of diisobutylphenoxypolyethoxyethanol described inUnited States Patent No. 2,752,284, alkylated aryl polyether alcohols,sodium alkylaryl polyether sulfates, and nonylphenoxypolyethoxyethanol.

It is preferred that a suitable plasticizer or humectant be added to thewater soluble vehicle to render the unmoistened sheet material morepliable and less likely to cause damage to any body tissue with which itmay come in contact. Suitable materials for this purpose are glycerol,sorbitol, polyethylene :glycols of high molecular weight and otherbland, non-deleterious, hygroscopic liquids which are compatible withthe film-forming material. The weight ratio of glycerol to vehicle maybe as much as 1213 or as little as 1:3. Larger amounts of glycerol arenot readily compatible with the vehicle proper and effective use, andwhich is without deleterious eiiect on the tissues with which it mayremain in contact.

According to the present invention the spermicidal manufacture comprisesa non-deleterious, bland mass, which is soluble in the body fluidsavailable in the vaginal cavity at a controlled rate of solution andwhich incorporates within it an effective amount of a spermicide,together, if desired, with a suitable humectant or plasticizing agentfor the mass to maintain the mass in a more pliable, less rigidcondition. The spermicidal manufacture is formed into sheets or foams insuch a manner that it has an extremely large surface area with respectto its mass, thereby increasing not only the rate at which it may bedissolved on contact with the body fluids, but also rendering the massmore pliable and less likely to cause damage to the tissues with whichit comes in contact.

The water soluble solid material which forms the vehicle for thespermicide and which forms the mass is a bland, non-deleterious, solid,tilm forming material, which is readily soluble in water and the bodyfluids with which it comes in contact within the vaginal cavity. Amongthe soluble materials which havebeen found suitable are the variousviscosity grades of sodium carboxymethylcellulose and methylcellulose.The sodium carboxymethylcellulose and methylcellulose used are of gradehaving a viscosity of from 25 to 10,000 centipoises per second in a 2%aqueous solution at 25 'C., and preferably such that a 2% by weightsolution in water at 25 C. has a viscosity of from 25 to 50 centipoisesper second, although other grades with similarly measured viscosities oftrom 50 to 10,000 centipoises per second are usable in certainformulations. Alternatively, they may be employed as vehicles, ifdesired, other water soluble nonputrefying, bland, film-forming, sol-idmaterials such as alginates, cellulose acetate, sorbate, and polyvinylalcohol (4-6 c.p.s.).

The water soluble vehicle is dissolved and mixed with and smalleramounts of glycerol do not produce the desired flexibility.

The solubility of the composition and articles of the present inventionin water and body fluids may be controlled by the presence in thevehicle of urea. The amount of urea should be such that a 3-inch squarefilm of the vehicle will dissolve in water at 37 C. in less thanseconds. The weight ratio of urea to vehicle may be as much as 1:3 or aslittle as 1:4. If the ratio of urea to vehicle is greater than 1:3,discontinuity may appear in the cast film. It the ratio of urea tovehicle is less than 124, the rate of solubility may be too slow.

The spermicidal manufacture may be formed as a filmlike sheet, or as asheet of foam, but in any event has an extremely large ratio of surfaceto volume so that it has a large surface which may be acted upon by thesolvent fluids to speed the process of dissolution upon contact with thevaginal fluids.

'In use, a suitable quantity of the sheet-like material comprising thewater soluble sheet containing the spermicide is compacted, either byrolling or by crumpling, and is introduced into the vaginal cavity andimmediately begins to dissolve and thus provides a viscous, retainedgel, having effective spermicidal activity, on the vaginal Walls.

In general, the material of the present invention comprises a sheet ofthe water soluble vehicle, either sodium carboxymethylcellulose ormethylcellulose. The sodium carboxymethylcellulose or methylcellulosewhich forms the vehicle is preferably dissolved in water to form asolution containing from 0.5% to 12.0% of vehicle solids, together withurea, a humectant such as glycerol, ethylene glycol or sorbitol and aspermicide in the proportions described above.

Where the sheet material is to be in the form of a film, the solutionmay be poured or otherwise fed onto a heated surface to the correctthickness to give the desired film thickness after drying, and the wateris then evaporated by gently heating of the support and the solutioncarried thereby. The solution is deposited in such in the solu- 1grams---inches square 0 carboxying:

The ratio of the working examples and the process by ing spec surface,as is customary The ratio of glycerol (or the follow y be cast and driedupon a lar g of continuous webs' of film. re of the present inventionylene glycol) do 220 the dried film to sodium carbox The ratio of urea tum carboxymethylcellulose ch the spermicidal materials of the ither thenon-foamed or the foamed g a polished in whi y be prepared,

will function as foaming agents ng now in detail to various mi1liliters46.2

solution is dried to form a film 3 rri Conveniently, e

A spermicide manufactu This Refe

agents and tion described sheet-like material rna heated cylinder havinin connection with the castin is made from a water solution comprisSodium carboxymethylcellulose mill NonylphenoxypolyethoxyethanolGlycerine (or polyeth Urea Water and about 0.005 inch in thickness.spermicide present in methylcellulose is methylcellulose is also 1:3.

is about 1:1.36.

of the manner present invention ma which they may be prepared 20polyethylene glycol) to sodi will be apthe boiling point is a sheet,relatively tion, while its other to assist in the its ingredients, afterThe heated surface is just slightly below e foam is destro dded strengthto the 15 the sheet or film is dried goven or chamber. In the ying, thedried film will have a h to 0.0075 inch and which apidly than filmshaving a greater Sheets of dried foamed material absorb moisture more 5supple and in many cases may reason. Such foams or foamed lently beatingair into the prising all of aterial is poured out onto a hot yeventually be separated, after is dried.

yed immediately adjagive a Thereafter,

, the preferable form inch to 0.240 inch thickness) which has ycontinuous and not interru -like or cellular forma surface exhibits thenormal appearance of a dried foam.

Foaming agents may of course be used manufacture of a foamed spermicide.

ermicides are surface active 2 thickness that after dr thickness of from0.001 inc will dissolve more I thickness.

be preferred for this sheet may be produced by vio prepared solution comwhich the foamed m surface from which it ma of water so that th cent thesupporting surface to sheet as a whole.

in any conventional dryin case of a foam thin (from 0.005

one of its faces substantiall ed by any foam 0 050 3 730 0000 mnmnohw 000 0 2410 0 05 2 L09 11112 3 L1L 1111 6 210 2 11112 7 2 10w 2 n 3 n 4 n n0 5 0 024: 0 fi v0 332 0 05 0 2410 0000 m. 1 0 .1 1111 2 1111 2 L0 211112 3111 2 m 5 3 5 mw73 0 0 0 331." 0 05 0 2410 000 w w 0 0 .0 nlmmmlL W 1 .1 1111 A 2 L0 9 11112 3L1 2 n 11 5 0060 2410 m005 0m2410 000w 0 m 2 L0 2 11112 2L0 2 11112 M 3 L1 2 n 0 0 000 3445 0 05 0 2410 M000m m 2 m 43 0 11127 3 2 10 211112 4. 311 2 1 0 0 000 3465 0 06 0 2410 000 n m N m 432 11117 M 2 10 2 11112 Q 4 31 m 0 000 KU 0 000 mmeo wa a 005 0 WJAJO 0 00 m 2 4; 1 111 7 8 2 13 1 .111 7 0 2 L0 2 11112 1 4 3 L 0005 mnwnm ro 0 005 34 5 0 030 m m23w0 0 00 N. r 0 050 53 0 0 0 0 n 73100 050 m 5450 0 %5 m 5 215 lflflmlnu w 5 3 5 1 115 m 022 n 1.3115 3 2 0 n0 050 2410 0 060 5110 0 300 m 3320 0 5 0 3410 2 102 11112 5 5 215 123157 0 3 3 5 113 .15 8 2 .0 2 11112 1 P| 2 1 u h 3 0 n 1 n u 0 0 0 2415 0000 MOO O m 535 0 003410 b .2... 6. 0: i 1 11 4 l 6 s 1 5 1 1 1 1 1 m 342 052 1 M lflll MM 2 0 211112 n n 1 m 5 um5 m23m0 0 0%0 m0000 m 244 m nn n 0 .0 113 L 3 5 2 .5 5 4 L1 1111 n n n 00 1 1 1 2 v 1 n n u n e nnnu6 u n n e a n h n a n n n n a n n a u 0 o o o 0 P D. D. .1 1 1 .r. t. tt H D 1 n 1 D l MT" m "II" w e n n 0 0 m I "II nh f M n mM um m wm rm 5mm i y l 1 1 6M" o. c 0 9R m o n 0 0w ent w m we m n E mm "wh s N mm mmpm mamm" m m m m mm mmIomm m m m mm 0 1H h SM O 1 u h S 0 f h S 6 1 1 a1 y a t h a N n by. m N H t V.r. N H 1 r m 0H by S 8 0! 92 9 .1 C0 .BXBMF 09 1 1c. yoh .6. oh m 0 V.oh 1c yoh 1 YO 11t m l l t .l th m i th mm 0i 0 0 t 0 .0 0 0 i m ay lm m m ay u m e m m new i r 1 mwl F 1 mi n d eyylv. Ie X 4 X ..X 0 4. .10 l. 0P c oD e 0D e o c we m 1 r m .1 m l nmrmeunm l nmflm e mwmpimm e fl u m w. m m mt .mned xm. eyy mnmm m m mmwu mum m m mr m mlm wmmar m m .mwmw mafia t um 06 r lnk CC I lnk 09 l n a81min n We d .vi n l vi s an nyeld vi s m1 w vi ss wL h e hh fi wl h e"h wl .t e ....hiS a SS G 8 1 h 8 06 1 u 4.. M m1 u mt. F 10 U m .0 1 ut 00 myr ma rv m v.r l a rv v.r a rv m myr a v l e e k l 1 mm aamwwm mwm mwmmwm a wa mammam a mem w m m m d6 .1 h 0 6 H h 0 d a efi .0 .10 1TO 11 1 lr h O 1 1 .10. 0 1f 1 1 h sMoUDNsAWoUsT sMoUDNsAwGusrsMoUDNsAWGUsr sMGUDNsAWGPwTT readily, films are more Which the foam orsheet preferably heated preciated that many active sp amples are given.These examples set forth specific solutions from which the articles ofthe present invention may be produced by evaporation of water inaccordance with the procedures described above. In each instance, thecomposition includes sodium carboxymethylcellulose or methylcellulose asa vehicle, together with urea and other ingredients. The quantitiesgiven are by weight and are based upon the grams used with 100 grams ofwater.

The above compositions were tested for spermicidal eifectiveness, themethod followed being that described in A Method of Testing the Relativespermicidal Effectiveness of Contraceptives, and Its Application to TenCommercial Products, Human Fertility, (4)-97, 1940, by R. L. Brown andC. I. Gamble.

In all instances the materials Were instantly spermicidal at dilutionsof 20 times (8/ 20).

Where the sheet-like material is in the form of a foam the area of thefilm-sheet, in square inches, should be at least 500 and preferably 1000times or more the thickness of the film, while with a vigorously beatenfoam, the area may be as small as or smaller than ten times thethickness of the material. Where a low concentration of spermicideoccurs in the vehicle, this ratio will generally be larger than withhigher concentnations, but with an unfoamed film 0.005 inch thick thatcontains about 14% of the spermicide, the area for a single use would beof the order of 9 to 16 square inches. With a film Which had aconcentration of 14% of spermicide and a thickness of 0.240 inch, about2.5 square inches of the material should be used.

The spermicidal film or foamed material of the present invention lendsitself readily to easy, inexpensive packaging, and a sufficient amountfor a single use may be enclosed and hermetically sealed in an envelopeof thermoplastic sheet material, such as polyethylene envelopes, inwhich case the material need not be completely dried, thereby partiallyeliminating the need for any hu-mectant, and at the same time increasingthe rapidity with which the dissolution of the material may start afterapplication.

The invention in its broader aspects is not limited to the specificsteps, processes and compositions shown and described but departures maybe made therefrom within the scope of the accompanying claims withoutdeparting from the principles of the invention and without sacrificingits chief advantages.

This application is a continuation-in-part of Serial No. 597,861, filedJuly 16, 1956, and 690,452, filed October 16, 1957, both now abandoned.

What is claimed is:

*1. A spermicidal sheet-like material comprising a sheet ofnon-deleterious, water soluble sodium carboxymethylcellulose, at least 5milligrams of nonylphenoxypolyethoxyethanol, from about 20% to about 25%by weight of urea based on vehicle solids and from about 25 to about 45%by weight of glycerol.

2. A spermicidal material as claimed in claim 1 in which the area of thesheet is at least 10 times as great as its thickness.

3. A spermicidal material as claimed in claim 1 in which the sheetmaterial is a foamed material.

4. A spermicidal material as claimed in claim 1 in which the sheet isfrom 0.001 to 0.0075 inch thick.

5. A spermicidal material as claimed in claim 1 in which the sheet isfrom 0.005 to 0.240 inch thick and is formed from a foam.

6. A spermicidal sheet like material comprising a sheet ofnon-deleterious Water soluble, carboxymethylcellulose, containing from20% to 25% by weight of urea and from 1% to by weight based on thecarboxymethylcellulose of a spermicide selected from the groupconsisting of alkylated aryl polyether alcohols and a sodium alkylarylpolyether surfates and also containing about 25 to 40% by weight basedon the carboxymethylcell-ulose of a humectant.

'7. A spermicidal sheet-like material as claimed in claim 6 in which thehumectant is glycerol.

References Cited in the file of this patent UNITED STATES PATENTS2,484637 Mattocks et al Oct. 11, 1949 2,563,593 Engel Aug. 7, 19512,602,042 Abbott July 1, 1952 2,693,438 Ward Nov. 2, 1954 FOREIGNPATENTS 150,013 Australia Feb. 12, 1953 OTHER REFERENCES Diserens: TheChemical Technology of Dyeing and Printing, Reinhold Publ. Co., New York(1948), p. 8.

1. A SPERMICIDAL SHEET-LIKE MATERIAL COMPRISING A SHEET OFNON-DELETERIOUS, WATER SOLUBLE SODIUM CARBOXYMETHYLCELLULOSE, AT LEAST 5MILLIGRAMS OF NONYLPHENOXYPOLYETHOXYETHANOL, FROM ABOUT 20% TO ABOUT 25%BY WEIGHT OF UREA BASED ON VEHICLE SOLIDS AND FROM ABOUT 25% TO ABOUT45% BY WEIGHT OF GLYCEROL.